Quality Control Symposium Examines Mechanisms of Ubiquitin-Dependent Protein Degradation

Like any successful factory, cells perform quality control. Explore this topic at the Quality Control Symposium led by Tom Rapoport, Harvard Medical School/HHMI, and Brenda Schulman, Max Planck Institute of Biochemistry. Both Rapoport and Schulman use multidisciplinary approaches to define intricate pathways, and ultimately use purified proteins to recapitulate how the ubiquitin-proteasome system marks molecules and shuttles them off for degradation and disposal.

“A good example of this process is how the cell rids itself of misfolded endoplasmic reticulum (ER) proteins,” Rapoport said. “These proteins are transported back into the cytosol, poly-ubiquitinated, extracted from the ER membrane, and degraded by the proteasome, a pathway termed ER-associated protein degradation (ERAD),” he explained.

Little is known about this quality control pathway when compared with translocation in the other direction, the pathway that moves proteins into the ER. Rapoport plans to discuss recent findings that reveal how ubiquitin-gated protein channels open up in the ER membrane to create a hole through which misfolded proteins can be pulled into the cytosol.

In addition to crucial roles in eliminating misfolded or damaged proteins, Schulman points out that “the ubiquitin-proteasome system also often regulates pathways requiring precise timing, through the rapid elimination of proteins once their job is complete.” One such process is cell division. For example, progression through mitosis, exit from mitosis, and the G1 phase are regulated by sequential ubiquitin tagging of a series of cell cycle regulators by the massive molecular machine Anaphase Promoting Complex, also known as APC/C. Schulman plans to discuss how the dynamic catalytic components are distinctly hijacked and dramatically reconfigured for stepwise progression through different stages of mitosis.

Symposium 6, Quality Control, will be held Wednesday, December 6, at 11:20 am.

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Mary Spiro is ASCB's Strategic Communications Manager.